Warburg effect regulated by amphiregulin in the development of colorectal cancer.
Warburg effect regulated by amphiregulin in the development of colorectal cancer.
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DOI：
10.1002/cam4.416
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发表时间：
2015-04
期刊：
影响因子：
4
通讯作者：
Miyamoto, Shingo
中科院分区：
文献类型：
--
作者：
Nam, Sung Ouk;Yotsumoto, Fusanori;Miyata, Kohei;Fukagawa, Satoshi;Yamada, Hiromi;Kuroki, Masahide;Miyamoto, Shingo
结直肠癌（Colorectal cancer，CRC）是世界范围内发病率和死亡率最高的恶性肿瘤之一。双调蛋白（AREG）是表皮生长因子家族的成员，是CRC治疗的合理靶点，对肿瘤形成的三维结构至关重要。为了克隆与AREG表达增加相关的基因，我们在进行二维（2DC）和三维培养（3DC）的两种CRC细胞系中进行了cDNA微阵列分析。选择与2DC相比在3DC中上调（>2.0倍）和下调（<0.5倍）的基因。基于京都基因和基因组百科全书（KEGG）途径数据库使用大卫的途径分析揭示了参与糖酵解的许多基因。在CRC细胞中，葡萄糖升高GLUT 1和AREG的表达以及缺氧诱导因子1（HIF-1）荧光素酶报告基因启动子的活性。AREG表达的抑制减少了葡萄糖的摄取和乳酸的产生。荧光素酶分析确定了起始位点上游-130和-180 bp之间的AREG表达的关键调控区，其中包含碳水化合物反应元件（ChoRE）。Max-like protein X（MLX）与ChoRE结合，促进AREG的表达。总之，这些数据表明，AREG通过激活瓦尔堡效应在CRC的发展中起关键作用。
Colorectal cancer (CRC) is one of the most frequently occurring cancers with high morbidity and mortality worldwide. Amphiregulin (AREG), a member of the epidermal growth factor family and a rational target for CRC therapy, is essential for the three-dimensional structure of tumor formation. To clone the genes associated with increased AREG expression, we performed a cDNA microarray analysis in two CRC cell lines undergoing two-dimensional (2DC) and three-dimensional culture (3DC). Upregulated (>2.0-fold) and downregulated (<0.5-fold) genes in 3DC compared with 2DC were selected. Pathway analysis using DAVID based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway databases revealed a number of genes involved in glycolysis. In CRC cells, glucose elevated the expression of GLUT1 and AREG as well as the activity of the hypoxia-inducible factor 1 (HIF-1) luciferase reporter promoter. The suppression of AREG expression reduced the uptake of glucose and production of lactate. Luciferase assay identified a critical regulatory region for AREG expression between −130 and −180 bp upstream of the start site, which contained a carbohydrate response element (ChoRE). Max-like protein X (MLX) bound to ChoRE and enhanced the expression of AREG. Together these data suggest that AREG plays a pivotal role in the development of CRC through activation of the Warburg effect.
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影响因子：
168.9
作者：
Cunningham, David;Atkin, Wendy;Starling, Naureen
通讯作者：
Starling, Naureen
影响因子：
15.9
作者：
Denechaud, Pierre-Damien;Bossard, Pascale;Postic, Catherine
通讯作者：
Postic, Catherine
TXNIP调节人类的外周葡萄糖代谢。
影响因子：
15.8
作者：
Parikh, Hemang;Carlsson, Emma;Chutkow, William A.;Johansson, Lovisa E.;Storgaard, Heidi;Poulsen, Pernille;Saxena, Richa;Ladd, Christine;Schulze, P. Christian;Mazzini, Michael J.;Jensen, Christine Bjorn;Krook, Anna;Bjornholm, Marie;Tornqvist, Hans;Zierath, Juleen R.;Ridderstrale, Martin;Altshuler, David;Lee, Richard T.;Vaag, Allan;Groop, Leif C.;Mootha, Vamsi K.
通讯作者：
Mootha, Vamsi K.
影响因子：
29.4
作者：
Berasain, C;García-Trevijano, ER;Avila, MA
通讯作者：
Avila, MA
影响因子：
11.2
作者：
Buzzai, Monica;Jones, Russell G.;Thompson, Craig B.
通讯作者：
Thompson, Craig B.